Resveratrol Triggered the Quick Self-Assembly of Gallic Acid into Therapeutic Hydrogels for Healing of Bacterially Infected Wounds

Programing self-assembly of naturally bioactive molecules has been a wide topic of great significance for biomedical uses. Despite the fact that plant-derived polyphenols with catechol or pyrogallol moieties have been widely studied to construct nanocomplexes or nanocoatings via self-polymerization, there is no report on the self-assembly of these polyphenols into therapeutic hydrogels for potential applications. Here, we reported that adding a very small amount of resveratrol (Res) into the gallic acid (GA) aqueous solution could trigger the quick self-assembly of GA to form a fibrous hydrogel within 5 min through hydrogen bonds and π-π interactions. The length of GA/Res (GR) fibrils in gels varied from 100 to 1000 microns, with a diameter of around 1 μm. Notably, these GR hydrogels showed excellent colloid stability, providing better slow release and outstanding biocompatibility. Also, in vivo experiments indicated the hydrogels had high antibacterial effects and excellent wound healing capabilities in a total skin defect model via regulating the expression of inflammatory factors (IL-6, IL-1β, and TNF-α) due to the release of therapeutic agents (GA and Res) into the matrix. Overall, our results provide a new strategy to accelerate self-assembly of GA by adding Res to form hydrogels, which is further proved as a promising therapeutic carrier for wound healing.